Proposed is a three part study of infarct expansion, the regional thinning and dilatation that may develop early after acute myocardial infarction and lead to overall cardiac dilatation, rupture and late aneurysm formation. In the first phase, specific determinants of expansion will be defined including infarct size, extent of transmurality, age of infarction, the development of fibrosis and fundamental mechanisms within the infarct zone which account for expansion. In the second phase, consequences of expansion will be studied with reference to the development of hypertrophy in noninfarcted myocardium. In the third phase, studies will be performed to determine whether infarct expansion can be altered. A rat infarct model will be used in which left coronary ligation produces a large percentage of anterior transmural infarcts. Morphologic studies will be performed on hearts with infarcts of varying ages arrested in diastole and sliced transversely. From histologic sections infarct expansion will be quantified, infarct size and murality determined, and histopathologic features of healing defined. Coincidently, synthesis of collagen (incorporation of proline into collagen and conversion of proline to hydroxy proline) will be studied biochemically. The effect of infarct expansion on hypertrophy of noninfarcted myocardium will be assessed by direct measurement of noninfarcted left ventricular mass, and RNA content per unit of myocardial mass. Interventions to alter the course of expansion will be tested in matched control and treatment groups of animals with infarction. Included will be interventions likely to increase expansion (exercise, afterload stress, steriods) and ones with potential for decreasing expansion (propranolol, mechanical unloading, and exercise preconditioning). The long term objective is to obtain information on the causes and consequences of a phenomenon which occurs after myocardial infarction and may contribute to poor early and late outcome. Moreover, it is anticipated that the intervention studies proposed will not only shed light on the pathophysiology of expansion but also identify potential approaches to therapy which could be translated into the human setting.